WO2003003006A3 - New potent, selective and non toxic c-kit inhibitors - Google Patents

New potent, selective and non toxic c-kit inhibitors Download PDF

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Publication number
WO2003003006A3
WO2003003006A3 PCT/IB2002/003296 IB0203296W WO03003006A3 WO 2003003006 A3 WO2003003006 A3 WO 2003003006A3 IB 0203296 W IB0203296 W IB 0203296W WO 03003006 A3 WO03003006 A3 WO 03003006A3
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WO
WIPO (PCT)
Prior art keywords
selective
non toxic
kit
kit inhibitors
new potent
Prior art date
Application number
PCT/IB2002/003296
Other languages
French (fr)
Other versions
WO2003003006A2 (en
Inventor
Alain Moussy
Patrice Dubreuil
Olivier Hermine
Original Assignee
Ab Science
Inst Nat Sante Rech Med
Univ Paris Descartes
Centre Nat Rech Scient
Assist Publ Hopitaux De Paris
Alain Moussy
Patrice Dubreuil
Olivier Hermine
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ab Science, Inst Nat Sante Rech Med, Univ Paris Descartes, Centre Nat Rech Scient, Assist Publ Hopitaux De Paris, Alain Moussy, Patrice Dubreuil, Olivier Hermine filed Critical Ab Science
Priority to US10/482,037 priority Critical patent/US7727731B2/en
Priority to DE60223063T priority patent/DE60223063T2/en
Priority to EP02755511A priority patent/EP1434991B1/en
Priority to CA002452368A priority patent/CA2452368A1/en
Priority to JP2003509139A priority patent/JP2005500041A/en
Publication of WO2003003006A2 publication Critical patent/WO2003003006A2/en
Publication of WO2003003006A3 publication Critical patent/WO2003003006A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/54—Interleukins [IL]
    • G01N2333/5403—IL-3
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/715—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Cell Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The present invention relates to a screening method allowing the identification and selection of compounds targeting the transphosphorylase (also called phosphotransferase) domain of c-kit, more particularly compounds selected to be potent inhibitors of constitutively activated c-kit, while being unable to inhibit other activation pathways such as for example the pathways leading to death of IL-3 dependent cells cultured in presence of IL-3.
PCT/IB2002/003296 2001-06-29 2002-06-28 New potent, selective and non toxic c-kit inhibitors WO2003003006A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US10/482,037 US7727731B2 (en) 2001-06-29 2002-06-28 Potent, selective and non toxic c-kit inhibitors
DE60223063T DE60223063T2 (en) 2001-06-29 2002-06-28 C-KIT INHIBITORS
EP02755511A EP1434991B1 (en) 2001-06-29 2002-06-28 New potent, selective and non toxic c-kit inhibitors
CA002452368A CA2452368A1 (en) 2001-06-29 2002-06-28 New potent, selective and non toxic c-kit inhibitors
JP2003509139A JP2005500041A (en) 2001-06-29 2002-06-28 Potent, selective and non-toxic C-KIT inhibitor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US30140401P 2001-06-29 2001-06-29
US60/301,404 2001-06-29

Publications (2)

Publication Number Publication Date
WO2003003006A2 WO2003003006A2 (en) 2003-01-09
WO2003003006A3 true WO2003003006A3 (en) 2004-04-29

Family

ID=23163195

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2002/003296 WO2003003006A2 (en) 2001-06-29 2002-06-28 New potent, selective and non toxic c-kit inhibitors

Country Status (7)

Country Link
US (1) US7727731B2 (en)
EP (1) EP1434991B1 (en)
JP (1) JP2005500041A (en)
AT (1) ATE376182T1 (en)
CA (1) CA2452368A1 (en)
DE (1) DE60223063T2 (en)
WO (1) WO2003003006A2 (en)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004537542A (en) * 2001-06-29 2004-12-16 アブ サイエンス Use of a tyrosine kinase inhibitor for treating inflammatory bowel disease (IBD)
US7727731B2 (en) 2001-06-29 2010-06-01 Ab Science Potent, selective and non toxic c-kit inhibitors
DK1401415T3 (en) * 2001-06-29 2006-10-16 Ab Science Use of N-phenyl-2-pyrimidinamine derivatives for the treatment of inflammatory diseases
CA2452366A1 (en) * 2001-06-29 2003-01-16 Ab Science Use of potent, selective and non toxic c-kit inhibitors for treating tumor angiogenesis
CA2452371A1 (en) 2001-06-29 2003-01-09 Ab Science Use of tyrosine kinase inhibitors for treating allergic diseases
EP1461032B1 (en) * 2001-09-20 2008-07-16 AB Science Use of c-kit inhibitors for promoting hair growth
JP2005511506A (en) * 2001-09-20 2005-04-28 アブ サイエンス Use of a potent, selective and non-toxic c-kit inhibitor for treating interstitial cystitis
JP2005526048A (en) * 2002-02-27 2005-09-02 アブ サイエンス Methods of using tyrosine kinase inhibitors for treating CNS diseases
US20050239852A1 (en) 2002-08-02 2005-10-27 Ab Science 2-(3-aminoaryl)amino-4-aryl-thiazoles and their use as c-kit inhibitors
US8450302B2 (en) 2002-08-02 2013-05-28 Ab Science 2-(3-aminoaryl) amino-4-aryl-thiazoles and their use as c-kit inhibitors
DE602004013283D1 (en) * 2003-02-27 2008-06-05 Ab Science DIAGNOSTIC METHOD OF MASTO CYTOSIS
BRPI0415467A (en) 2003-10-23 2006-12-19 Ab Science 2-aminoaryloxazole compounds for the treatment of disease
WO2005102318A1 (en) * 2004-04-20 2005-11-03 Ab Science Use of c-kit inhibitors for treating hiv related diseases
WO2005102326A2 (en) * 2004-04-23 2005-11-03 Ab Science Use of c-kit inhibitors for treating renal diseases
EP1746990A1 (en) * 2004-05-18 2007-01-31 AB Science Use of mast cells inhibitors for treating patients exposed to chemical or biological weapons
WO2006106437A2 (en) 2005-04-04 2006-10-12 Ab Science Substituted oxazole derivatives and their use as tyrosine kinase inhibitors
KR20090110851A (en) 2007-02-13 2009-10-22 에이비 사이언스 Process for the synthesis of 2-aminothiazole compounds as kinase inhibitors
CA2840029C (en) 2011-07-27 2021-07-20 Ab Science Oxazole and thiazole derivatives as selective protein kinase inhibitors (c-kit)
EP3942045A1 (en) 2019-03-21 2022-01-26 Onxeo A dbait molecule in combination with kinase inhibitor for the treatment of cancer
EP4054579A1 (en) 2019-11-08 2022-09-14 Institut National de la Santé et de la Recherche Médicale (INSERM) Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
WO2022173861A1 (en) * 2021-02-09 2022-08-18 Jasper Therapeutics, Inc. Modified stem cell compositions and methods for use
WO2023159136A2 (en) * 2022-02-18 2023-08-24 Dana-Farber Cancer Institute, Inc. Epitope engineering of cell-surface receptors

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0564409A1 (en) * 1992-04-03 1993-10-06 Ciba-Geigy Ag Pyrimidin derivatives and process for their preparation
WO1998055152A1 (en) * 1997-06-06 1998-12-10 Baylor College Of Medicine The mast cell secretory machine as a target for anti-allergy drug development
WO1999003854A1 (en) * 1997-07-18 1999-01-28 Novartis Ag Crystal modification of a n-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use
WO2001027081A1 (en) * 1999-10-13 2001-04-19 Boehringer Ingelheim Pharma Kg 6-position substituted indoline, production and use thereof as a medicament

Family Cites Families (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3467666A (en) * 1966-11-07 1969-09-16 Geigy Chem Corp 2-substituted aminothiazoles
US3558653A (en) * 1968-05-20 1971-01-26 Searle & Co Dialkylaminoalkyl-indolines
US3725403A (en) * 1970-10-20 1973-04-03 Squibb & Sons Inc Benzothiazine derivatives
US4438267A (en) * 1980-11-11 1984-03-20 Daluge Susan M Monoheteroring compounds and their use
GB8913708D0 (en) 1989-06-14 1989-08-02 Unilever Plc Cosmetic composition
US5308839A (en) 1989-12-04 1994-05-03 The Research Foundation Of State University Of New York Composition comprising non-steroidal anti-inflammatory agent tenidap and effectively non-antibacterial tetracycline
US5521184A (en) * 1992-04-03 1996-05-28 Ciba-Geigy Corporation Pyrimidine derivatives and processes for the preparation thereof
US5639757A (en) * 1995-05-23 1997-06-17 Pfizer Inc. 4-aminopyrrolo[2,3-d]pyrimidines as tyrosine kinase inhibitors
US5880141A (en) * 1995-06-07 1999-03-09 Sugen, Inc. Benzylidene-Z-indoline compounds for the treatment of disease
GB9523675D0 (en) * 1995-11-20 1996-01-24 Celltech Therapeutics Ltd Chemical compounds
JP2000508894A (en) * 1996-04-10 2000-07-18 ヒューマン ジノーム サイエンシーズ，インコーポレイテッド Extracellular / epidermal growth factor HCABA58X
GB9622363D0 (en) 1996-10-28 1997-01-08 Celltech Therapeutics Ltd Chemical compounds
EP0968304A1 (en) 1997-02-11 2000-01-05 Merck & Co., Inc. Identification of inhibitors of protein tyrosine kinase 2
CN1134439C (en) 1997-03-19 2004-01-14 艾博特股份有限两合公司 Pyrrolo [2,3D] pyrimidines and their use as tyrosine kinase inhibitors
EP0984930B1 (en) 1997-05-07 2005-04-06 Sugen, Inc. 2-indolinone derivatives as modulators of protein kinase activity
US6114371A (en) * 1997-06-20 2000-09-05 Sugen, Inc. 3-(cyclohexanoheteroarylidenyl)-2-indolinone protein tyrosine kinase inhibitors
EP1012151B1 (en) 1997-09-02 2002-08-07 Bristol-Myers Squibb Pharma Company Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone (crh) antagonists, useful for treating cns and stress-related disorders
GB9718913D0 (en) 1997-09-05 1997-11-12 Glaxo Group Ltd Substituted oxindole derivatives
US6133305A (en) * 1997-09-26 2000-10-17 Sugen, Inc. 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity
US5952374A (en) * 1997-09-29 1999-09-14 Protein Technologies International, Inc. Method for inhibiting the development of Alzheimer's disease and related dementias- and for preserving cognitive function
GB9721437D0 (en) 1997-10-10 1997-12-10 Glaxo Group Ltd Heteroaromatic compounds and their use in medicine
CA2333556A1 (en) 1998-05-27 1999-12-02 Sherwood L. Gorbach Isoflavonoids for treatment and prevention of migraine headaches
SK287132B6 (en) 1998-05-29 2009-12-07 Sugen, Inc. Pharmaceutical composition containing pyrrole substituted 2-indolinone, kit containing mentioned composition and use pyrrole substituted 2-indolinone
DE19824922A1 (en) 1998-06-04 1999-12-09 Boehringer Ingelheim Pharma Novel substituted indolinones, their preparation and their use as pharmaceuticals
RS50087B (en) 1998-06-19 2009-01-22 Pfizer Products Inc., Pyrolo (2,3-d) pyrimidine compounds
ATE371453T1 (en) 1998-08-13 2007-09-15 Novartis Pharma Gmbh METHOD FOR TREATING OCCULAR NEOVASCULAR DISEASES
DE19844003A1 (en) 1998-09-25 2000-03-30 Boehringer Ingelheim Pharma New 3-aminomethylidene-2-indolinone derivatives useful as kinase inhibitors and antiproliferative agents e.g. for treating viral infections, tumors, inflammation or autoimmune disease
EP1141722A1 (en) 1998-12-31 2001-10-10 Sugen, Inc. Pyk2 (raftk) and inflammation
US6498176B1 (en) * 1999-03-04 2002-12-24 Smithklinebeecham Corporation 3-(anilinomethylene) oxindoles as protein tyrosine kinase and protein serine/threonine kinase inhibitors
US6245759B1 (en) * 1999-03-11 2001-06-12 Merck & Co., Inc. Tyrosine kinase inhibitors
NZ514711A (en) 1999-03-12 2004-02-27 Boehringer Ingelheim Pharma Compounds useful as anti-inflammatory agents
AU3770000A (en) 1999-03-24 2000-10-09 Sugen, Inc. Indolinone compounds as kinase inhibitors
US6989248B2 (en) 1999-05-06 2006-01-24 The Trustees Of Columbia University In The City Of New York Methods of use of compounds which inhibit the stem cell signaling pathway
DE19924401A1 (en) 1999-05-27 2000-11-30 Boehringer Ingelheim Pharma Novel substituted indolinones, their preparation and their use as pharmaceuticals
AU5636900A (en) * 1999-06-30 2001-01-31 Merck & Co., Inc. Src kinase inhibitor compounds
WO2001016130A1 (en) 1999-08-27 2001-03-08 Boehringer Ingelheim Pharma Kg Substituted indolinones as tyrosine kinase inhibitors
US6762180B1 (en) * 1999-10-13 2004-07-13 Boehringer Ingelheim Pharma Kg Substituted indolines which inhibit receptor tyrosine kinases
WO2001045689A2 (en) * 1999-12-22 2001-06-28 Sugen, Inc. Indolinone derivatives for modulation of c-kit tyrosine protein kinase
AU2511901A (en) 1999-12-23 2001-07-09 Universite De Geneve Basolateral sorting signal and inhibitors thereof
US6339100B1 (en) 1999-12-29 2002-01-15 The Trustees Of Columbia University In The City Of New York Methods for inhibiting mastocytosis
JP2003535038A (en) 1999-12-30 2003-11-25 スージェン・インコーポレーテッド 3-Heteroarylidenyl-2-indolinone compounds for modulating protein kinase activity and for use in cancer chemotherapy
AU3704101A (en) * 2000-02-17 2001-08-27 Amgen Inc Kinase inhibitors
US6420382B2 (en) * 2000-02-25 2002-07-16 Merck & Co., Inc. Tyrosine kinase inhibitors
AU2001237401B2 (en) 2000-03-01 2006-11-09 Janssen Pharmaceutica N.V. 2,4-disubstituted thiazolyl derivatives
US7087608B2 (en) 2000-03-03 2006-08-08 Robert Charles Atkins Use of PDGF receptor tyrosine kinase inhibitors for the treatment of diabetic nephropathy
MY128449A (en) 2000-05-24 2007-02-28 Sugen Inc Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives
MXPA03003703A (en) * 2000-10-27 2005-01-25 Novartis Ag Treatment of gastrointestinal stromal tumors.
NZ525334A (en) 2000-11-17 2005-07-29 Bristol Myers Squibb Co Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
JP2004518669A (en) 2000-12-20 2004-06-24 スージェン・インコーポレーテッド 4-Aryl substituted indolinone
WO2002072578A2 (en) 2001-03-08 2002-09-19 Millennium Pharmaceuticals (homo) piperazine substituted quinolines for inhibiting the phosphorylation of kinases
GB0108606D0 (en) 2001-04-05 2001-05-23 Novartis Ag Organic compounds
ATE331519T1 (en) * 2001-05-16 2006-07-15 Gpc Biotech Ag PYRIDYLPYRIMIDINE DERIVATIVES AS EFFECTIVE COMPOUNDS AGAINST PRION DISEASES
CA2452171A1 (en) * 2001-06-29 2003-01-09 Ab Science Use of potent, selective and non toxic c-kit inhibitors for treating mastocytosis
US20050176687A1 (en) * 2001-06-29 2005-08-11 Alain Moussy Use of tyrosine kinase inhibitors for treating autoimmune diseases
WO2003002105A2 (en) * 2001-06-29 2003-01-09 Ab Science Use of tyrosine kinase inhibitors for treating bone loss
DK1401415T3 (en) * 2001-06-29 2006-10-16 Ab Science Use of N-phenyl-2-pyrimidinamine derivatives for the treatment of inflammatory diseases
US20030091974A1 (en) * 2001-06-29 2003-05-15 Alain Moussy Method for screening compounds capable of depleting mast cells
CA2452366A1 (en) * 2001-06-29 2003-01-16 Ab Science Use of potent, selective and non toxic c-kit inhibitors for treating tumor angiogenesis
US7727731B2 (en) 2001-06-29 2010-06-01 Ab Science Potent, selective and non toxic c-kit inhibitors
CA2452371A1 (en) * 2001-06-29 2003-01-09 Ab Science Use of tyrosine kinase inhibitors for treating allergic diseases
JP2004537542A (en) * 2001-06-29 2004-12-16 アブ サイエンス Use of a tyrosine kinase inhibitor for treating inflammatory bowel disease (IBD)
WO2003002107A2 (en) * 2001-06-29 2003-01-09 Ab Science Use of tyrosine kinase inhibitors for treating multiple sclerosis (ms)
ATE530635T1 (en) * 2001-08-21 2011-11-15 Ventana Med Syst Inc METHOD AND QUANTIFICATION ASSAY FOR DETERMINING C-KIT/SCF/PAKT STATUS
JP2005507916A (en) 2001-09-20 2005-03-24 アブ サイエンス Use of potent, selective and non-toxic c-kit inhibitors for the treatment of bacterial infections
EP1461032B1 (en) 2001-09-20 2008-07-16 AB Science Use of c-kit inhibitors for promoting hair growth
JP2005511506A (en) * 2001-09-20 2005-04-28 アブ サイエンス Use of a potent, selective and non-toxic c-kit inhibitor for treating interstitial cystitis
JP2005511596A (en) * 2001-09-20 2005-04-28 アブ サイエンス Methods of using tyrosine kinase inhibitors for whitening human skin and treating diseases associated with melanocyte dysfunction
US7910586B2 (en) * 2002-01-04 2011-03-22 The Rockefeller University Compositions and methods for prevention and treatment of amyloid-β peptide-related disorders
WO2003062215A1 (en) 2002-01-25 2003-07-31 Kylix Pharmaceuticals B.V. 4(hetero-) aryl substituted (thia-/oxa-/pyra) zoles for inhibition of tie-2
JP2005526048A (en) * 2002-02-27 2005-09-02 アブ サイエンス Methods of using tyrosine kinase inhibitors for treating CNS diseases
US20050089838A1 (en) * 2002-06-28 2005-04-28 Alain Moussy Method for identifying compounds that specifically deplete mast cells
US20050239852A1 (en) * 2002-08-02 2005-10-27 Ab Science 2-(3-aminoaryl)amino-4-aryl-thiazoles and their use as c-kit inhibitors
WO2004062591A2 (en) * 2003-01-06 2004-07-29 Oregon Health And Science University Methods of treatment and diagnosis of kaposi's sarcoma (ks) and ks related diseases

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0564409A1 (en) * 1992-04-03 1993-10-06 Ciba-Geigy Ag Pyrimidin derivatives and process for their preparation
WO1998055152A1 (en) * 1997-06-06 1998-12-10 Baylor College Of Medicine The mast cell secretory machine as a target for anti-allergy drug development
WO1999003854A1 (en) * 1997-07-18 1999-01-28 Novartis Ag Crystal modification of a n-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use
WO2001027081A1 (en) * 1999-10-13 2001-04-19 Boehringer Ingelheim Pharma Kg 6-position substituted indoline, production and use thereof as a medicament

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MA Y ET AL: "INDOLINONE DERIVATIVES INHIBIT CONSTITUTIVELY ACTIVATED KIT MUTANTS AND KILL NEOPLASTIC MAST CELLS", JOURNAL OF INVESTIGATIVE DERMATOLOGY, NEW YORK, NY, US, vol. 114, no. 2, February 2001 (2001-02-01), pages 392 - 394, XP001127437, ISSN: 0022-202X *

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